title: Computational design of RNAs with complex energy landscapes.
abstract: RNA has become an integral building material in synthetic biology. Dominated by their secondary structures, which can be computed efficiently, RNA molecules are amenable not only to in vitro and in vivo selection, but also to rational, computation-based design. While the inverse folding problem of constructing an RNA sequence with a prescribed ground-state structure has received considerable attention for nearly two decades, there have been few efforts to design RNAs that can switch between distinct prescribed conformations. We introduce a user-friendly tool for designing RNA sequences that fold into multiple target structures. The underlying algorithm makes use of a combination of graph coloring and heuristic local optimization to find sequences whose energy landscapes are dominated by the prescribed conformations. A flexible interface allows the specification of a wide range of design goals. We demonstrate that bi- and tri-stable "switches" can be designed easily with moderate computational effort for the vast majority of compatible combinations of desired target structures. RNAdesign is freely available under the GPL-v3 license.
authors.affiliation: Department of Theoretical Chemistry, University of Vienna, Währingerstraße 17, A-1090 Wien, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Höner zu Siederdissen
authors.forename: Stefan
authors.initials: S
authors.lastname: Hammer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Abfalter
authors.forename: Ivo L
authors.initials: IL
authors.lastname: Hofacker
authors.forename: Christoph
authors.initials: C
authors.lastname: Flamm
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry; D059370:RNA Folding
chemical_list: D012313:RNA
keywords: RNA sequence design; graph coloring; inverse folding; multi-stable structures